High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity

Michael C. Haffner, Johannes Laimer, Alcides Chaux, Georg Schäfer, Peter Obrist, Andrea Brunner, Irmgard E. Kronberger, Klaus Laimer, Bora Gurel, Johann Benedikt Koller, Christof Seifarth, Bettina Zelger, Helmut Klocker, Michael Rasse, Wolfgang Doppler, Neil H. Bander

Research output: Contribution to journalArticle

Abstract

Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in prostate cancer as well as in the neo-vasculature of nonprostatic solid tumors. Here, we determined the expression pattern of PSMA in the vasculature of oral squamous cell carcinoma. Using a previously validated antibody, PSMA staining distribution and cyclooxygenase 2 (COX2) expression status was evaluated in a cohort of patients with squamous cell carcinoma of the oral cavity (n=96) using immunohistochemistry and was correlated with clinicopathological features as well as outcome. Twenty-four (25%) cases showed no detectable PSMA staining, 48 (50%) demonstrated positive immunoreactivity for PSMA in less than 50% of microvessels and 24 (25%) cases showed strong endothelial PSMA expression in more than 50% of tumor-associated microvessels. High endothelial PSMA expression was associated with greatly reduced survival (18.2 vs 77.3 months; P=0.0001) and maintained prognostic significance after adjusting for grade and stage in multivariate analysis (hazard ratio=2.19, P=0.007). Furthermore, we observed a strong association between endothelial PSMA and cancer cell-specific COX2 expression. In conclusion, we provide the first evidence for the prognostic significance of endothelial PSMA expression in oral squamous cell carcinoma and, suggest a potential interaction between arachidonic acid metabolites and endothelial PSMA expression in the tumor neo-vasculature.

Original languageEnglish (US)
Pages (from-to)1079-1085
Number of pages7
JournalModern Pathology
Volume25
Issue number8
DOIs
StatePublished - Aug 2012
Externally publishedYes

Fingerprint

Mouth
Squamous Cell Carcinoma
Neoplasms
Cyclooxygenase 2
Microvessels
human glutamate carboxypeptidase II
Staining and Labeling
Arachidonic Acid
Prostatic Neoplasms
Multivariate Analysis
Immunohistochemistry
Survival
Antibodies

Keywords

  • COX2
  • FOLH1
  • oral squamous cell carcinoma
  • prognosis
  • prostate-specific membrane antigen
  • PSMA
  • vasculature

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity. / Haffner, Michael C.; Laimer, Johannes; Chaux, Alcides; Schäfer, Georg; Obrist, Peter; Brunner, Andrea; Kronberger, Irmgard E.; Laimer, Klaus; Gurel, Bora; Koller, Johann Benedikt; Seifarth, Christof; Zelger, Bettina; Klocker, Helmut; Rasse, Michael; Doppler, Wolfgang; Bander, Neil H.

In: Modern Pathology, Vol. 25, No. 8, 08.2012, p. 1079-1085.

Research output: Contribution to journalArticle

Haffner, MC, Laimer, J, Chaux, A, Schäfer, G, Obrist, P, Brunner, A, Kronberger, IE, Laimer, K, Gurel, B, Koller, JB, Seifarth, C, Zelger, B, Klocker, H, Rasse, M, Doppler, W & Bander, NH 2012, 'High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity', Modern Pathology, vol. 25, no. 8, pp. 1079-1085. https://doi.org/10.1038/modpathol.2012.66
Haffner, Michael C. ; Laimer, Johannes ; Chaux, Alcides ; Schäfer, Georg ; Obrist, Peter ; Brunner, Andrea ; Kronberger, Irmgard E. ; Laimer, Klaus ; Gurel, Bora ; Koller, Johann Benedikt ; Seifarth, Christof ; Zelger, Bettina ; Klocker, Helmut ; Rasse, Michael ; Doppler, Wolfgang ; Bander, Neil H. / High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity. In: Modern Pathology. 2012 ; Vol. 25, No. 8. pp. 1079-1085.
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abstract = "Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in prostate cancer as well as in the neo-vasculature of nonprostatic solid tumors. Here, we determined the expression pattern of PSMA in the vasculature of oral squamous cell carcinoma. Using a previously validated antibody, PSMA staining distribution and cyclooxygenase 2 (COX2) expression status was evaluated in a cohort of patients with squamous cell carcinoma of the oral cavity (n=96) using immunohistochemistry and was correlated with clinicopathological features as well as outcome. Twenty-four (25{\%}) cases showed no detectable PSMA staining, 48 (50{\%}) demonstrated positive immunoreactivity for PSMA in less than 50{\%} of microvessels and 24 (25{\%}) cases showed strong endothelial PSMA expression in more than 50{\%} of tumor-associated microvessels. High endothelial PSMA expression was associated with greatly reduced survival (18.2 vs 77.3 months; P=0.0001) and maintained prognostic significance after adjusting for grade and stage in multivariate analysis (hazard ratio=2.19, P=0.007). Furthermore, we observed a strong association between endothelial PSMA and cancer cell-specific COX2 expression. In conclusion, we provide the first evidence for the prognostic significance of endothelial PSMA expression in oral squamous cell carcinoma and, suggest a potential interaction between arachidonic acid metabolites and endothelial PSMA expression in the tumor neo-vasculature.",
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AU - Laimer, Johannes

AU - Chaux, Alcides

AU - Schäfer, Georg

AU - Obrist, Peter

AU - Brunner, Andrea

AU - Kronberger, Irmgard E.

AU - Laimer, Klaus

AU - Gurel, Bora

AU - Koller, Johann Benedikt

AU - Seifarth, Christof

AU - Zelger, Bettina

AU - Klocker, Helmut

AU - Rasse, Michael

AU - Doppler, Wolfgang

AU - Bander, Neil H.

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